Evidence and implications of pre‐existing humoral cross‐reactive immunity to SARS‐CoV‐2

Nzoghe, Amandine Mveang; Essone, Paulin N.; Leboueny, Marielle; Siawaya, Anicet Christel Maloupazoa; Bongho, Eliode Cyrien; Ndjindji, Ofilia Mvoundza; Houechenou, Rotimi Myrabelle Avome; Agnandji, Selidji Todagbé; Siawaya, Joël Fleury Djoba

doi:10.1002/iid3.367

Cited by 29 publications

(28 citation statements)

References 13 publications

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“…As we confirmed the sensitivity of PBNA, high background levels (PBNI 50 of 100 to 250) in 5 out of 6 unexposed NHP serum samples, might be due to pre-exposure to other coronaviruses in their natural environment (which might have generated neutralizing antibodies). Couple of previous reports about preexisting humoral immunity to SARS-CoV-2 in humans support this explanation [31,32].…”

Section: Discussionsupporting

confidence: 63%

SARS-CoV-2 Spike Pseudoviruses: A Useful tool to study virus entry and address emerging neutralization escape phenotypes

Kalkeri

Cai

Lin

et al. 2021

Preprint

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SARS-CoV-2 genetic variants are emerging around the globe. Unfortunately, several SARS-CoV-2 variants, especially, variants of concern (VOC) are less susceptible to neutralization by the convalescent and post-vaccination sera, raising concerns of increased disease transmissibility and severity. Recent data suggests the SARS-CoV-2 neutralizing anti-body levels as a good correlate of vaccine mediated protection. However, currently used BSL3 based virus micro-neutralization (MN) assays are more laborious, time consuming and expensive, underscoring the need for BSL2 based, cost effective neutralization assays against SARS-CoV-2 variants. In light of this unmet need, we have developed a BSL2 pseudovirus based neutralization assay (PBNA) in cells expressing Angiotensin Converting Enzyme-2 (ACE2) receptor for SARS-CoV-2. The assay is reproducible (R2=0.96), demonstrates a good dynamic range and high sensitivity. Our data suggests that the biological Anti-SARS-CoV-2 research reagents such as NIBSC 20/130 show lower neutralization against B.1.351 RSA and B1.1.7 UK VOC, whereas a commercially available monoclonal antibody MM43 retains activity against both these variants. SARS-CoV-2 Spike Pseudovirus based neutralization assays for VOC would be useful tools to measure the neutralization ability of candidate vaccines in both preclinical models and clinical trials and further help develop effective prophylactic countermeasures against emerging neutralization escape phenotypes.

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Section: Discussionsupporting

confidence: 63%

SARS-CoV-2 Spike Pseudoviruses: A Useful tool to study virus entry and address emerging neutralization escape phenotypes

Kalkeri

Cai

Lin

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…As we confirmed the sensitivity of the PBNA, high background levels (PBNI 50 of 100 to 250) in five out of the six unexposed NHP serum samples might be due to pre-exposure to other coronaviruses in their natural environment (which might have generated neutralizing antibodies). Several previous reports regarding preexisting humoral immunity to SARS-CoV-2 in humans support this explanation [31,32].…”

Section: Discussionmentioning

confidence: 79%

SARS-CoV-2 Spike Pseudoviruses: A Useful Tool to Study Virus Entry and Address Emerging Neutralization Escape Phenotypes

et al. 2021

View full text Add to dashboard Cite

SARS-CoV-2 genetic variants are emerging around the globe. Unfortunately, several SARS-CoV-2 variants, especially variants of concern (VOCs), are less susceptible to neutralization by the convalescent and post-vaccination sera, raising concerns of increased disease transmissibility and severity. Recent data suggests that SARS-CoV-2 neutralizing antibody levels are a reliable correlate of vaccine-mediated protection. However, currently used BSL3-based virus micro-neutralization (MN) assays are more laborious, time-consuming, and expensive, underscoring the need for BSL2-based, cost-effective neutralization assays against SARS-CoV-2 variants. In light of this unmet need, we have developed a BSL-2 pseudovirus-based neutralization assay (PBNA) in cells expressing the human angiotensin-converting enzyme-2 (hACE2) receptor for SARS-CoV-2. The assay is reproducible (R2 = 0.96), demonstrates a good dynamic range and high sensitivity. Our data suggest that the biological Anti-SARS-CoV-2 research reagents such as NIBSC 20/130 show lower neutralization against B.1.351 SA (South Africa) and B.1.1.7 UK (United Kingdom) VOC, whereas a commercially available monoclonal antibody MM43 retains activity against both these variants. SARS-CoV-2 spike PBNAs for VOCs would be useful tools to measure the neutralization ability of candidate vaccines in both preclinical models and clinical trials and would further help develop effective prophylactic countermeasures against emerging neutralization escape phenotypes.

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“…Findings from previous studies using samples from Benin, Nigeria, and Ghana have led to speculation that malaria contributes to cross-binding antibodies or other humoral factors (19,20). An additional study in the country of Gabon, where malaria is highly endemic, found that 32 of 135 (23.7%) samples from 2014 were positive for SARS-CoV-2 antibodies using an NCP antigen serological assay, although the authors acknowledged that the cause of the cross-reactivity could not be isolated with certainty (37). Our current study found anti-Plasmodium IgG levels to be significantly higher in samples with false-positive SARS-CoV-2 results than in those with negative results.…”

Section: Discussionmentioning

confidence: 99%

Cross-Reactivity of Two SARS-CoV-2 Serological Assays in a Setting Where Malaria Is Endemic

et al. 2021

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Background: Accurate SARS-CoV-2 serological assays are critical for COVID-19 serosurveillance. However, previous studies have indicated possible cross-reactivity of these assays, including in malaria-endemic areas. Methods: We tested 213 well-characterized pre-pandemic samples from Nigeria using two SARS-CoV-2 serological assays: Abbott Architect IgG and Euroimmun NCP IgG assay, both targeting SARS-CoV-2 nucleocapsid protein. To assess antibody binding strength, an avidity assay was performed on these samples and on plasma from SARS-CoV-2 PCR-positive persons. Results: Thirteen (6.1%) of 212 samples run on the Abbott assay and 38 (17.8%) of 213 run on the Euroimmun assay were positive. Anti-Plasmodium IgG levels were significantly higher among false-positives for both Abbott and Euroimmun; no association was found with active P. falciparum infection. An avidity assay using various concentratIons of urea wash in the Euroimmun assay reduced loosely-bound IgG: of 37 positive/borderline pre-pandemic samples, 46%, 86%, 89%, and 97% became negative using 2M, 4M, 5M, and 8M urea washes, respectively. The wash slightly reduced avidity of antibodies from SARS-CoV-2 patients within 28 days of PCR confirmation; thereafter avidity increased for all urea concentrations except 8M. Conclusions: This validation found moderate to substantial cross-reactivity on two SARS-CoV-2 serological assays using samples from a malaria-endemic setting. A simple urea wash appeared to alleviate issues of cross-reactivity.

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Evidence and implications of pre‐existing humoral cross‐reactive immunity to SARS‐CoV‐2

Cited by 29 publications

References 13 publications

SARS-CoV-2 Spike Pseudoviruses: A Useful tool to study virus entry and address emerging neutralization escape phenotypes

SARS-CoV-2 Spike Pseudoviruses: A Useful tool to study virus entry and address emerging neutralization escape phenotypes

SARS-CoV-2 Spike Pseudoviruses: A Useful Tool to Study Virus Entry and Address Emerging Neutralization Escape Phenotypes

Cross-Reactivity of Two SARS-CoV-2 Serological Assays in a Setting Where Malaria Is Endemic

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